On September 19, 2011, NASA announced that Saint-Jacques would serve as an aquanaut aboard the Aquariusunderwater laboratory during the NEEMO 15 undersea exploration mission from October 17–30, 2011.[4] Delayed by stormy weather and high seas, the mission began on October 20, 2011.[5][6] On the afternoon of October 21, Saint-Jacques and his crewmates officially became aquanauts, having spent over 24 hours underwater. NEEMO 15 ended early on October 26 due to the approach of Hurricane Rina.[5]

Saint-Jacques completes the Bone Densitometer calibration in support of the Rodent Research-8 investigation during Expedition 57 at the Destiny lab

Saint-Jaques during his first spacewalk, on ISS Expedition 59

In May 2016 Saint-Jacques was selected as a member of ISS Expedition 58/59, which at the time was scheduled to start in November 2018.[7]

On 3 December 2018, Saint-Jacques launched to the ISS on board Soyuz MS-11, alongside commander Oleg Kononenko and fellow flight engineer Anne McClain.[8] He became a member of the Expedition 57 crew for two weeks before transferring to Expedition 58, which officially started on 20 December 2018 when the Expedition 57 crew left the station. Saint-Jacques, Kononenko and McClain subsequently transferred to Expedition 59 on 14 March 2019 with the arrival of Soyuz MS-12, and are scheduled to leave the ISS in July 2019.

On April 8, 2019, Saint-Jacques conducted his first spacewalk,[9] becoming the fourth Canadian astronaut to take part in an EVA and the first to do so in 12 years. The spacewalk lasted roughly seven hours.[10]